Grant: Project Grant

Protein folding and degradation are central to cell biology. An exquisite control of these processes is required to ensure the proper survival of the cell and the health of the organism. Protein misfolding and aggregation have been linked to a large number of diseases including cancer, aging, and neurodegeneration. Maintaining protein homeostasis in the cell is accomplished by two classes of proteins: (1) molecular chaperones that assist in protein folding and protein complex formation, and (2) proteolytic complexes that lead to the degradation of misfolded and destabilized proteins. The proposed project aims to investigate how protein homeostasis is maintained in the mitochondrion by the highly conserved ATP-dependent protease ClpXP. The mitochondrion is central for energy metabolism and other essential cellular processes such as the control of Ca2+ levels and apoptosis. Many diseases are related to the malfunctioning of the mitochondria caused by mitochondrial proteostatic stress. In this regard, ClpXP plays a critical role in cell signaling in several diseases including cancer. However, the mechanism of function of mitochondrial ClpXP is not known and is the subject of this grant application.